Apalutamide prolongs progression-free survival in prostate cancer

The addition of apalutamide to abiraterone acetate plus prednisone/prednisolone (AAP) reduced the risk of radiographic progression or death in men with metastatic castration-resistant prostate cancer (mCRPC) who had not received prior chemotherapy [1].

Both activated androgen receptors and elevated androgen production promote prostate cancer; therefore, treatment is directed towards both blocking androgen receptors and suppressing androgen production. Apalutamide is an androgen receptor inhibitor and abiraterone acetate is an androgen inhibitor that works via ligand suppression. Abiraterone acetate is administered in combination with either prednisone or prednisolone. The ACIS trial (NCT02257736) hypothesised that additional benefit could be conferred by combining these therapies.

Dr Dana Rathkopf (Memorial Sloan Kettering Cancer Center, New York, USA) shared the results of the phase 3, randomised, double-blind ACIS trial designed to compare radiographic progression-free survival (rPFS) in mCRPC patients receiving apalutamide in addition to AAP with rPFS in mCRPC patients with receiving placebo plus AAP. None of the 982 patients in the study had been previously treated with chemotherapy.

The primary endpoint was investigator-assessed rPFS over a time frame defined as time from randomisation until death, loss to follow-up, withdrawal of consent, or end of study, whichever occurred first, up to 5 years. Progression of soft tissue lesions was defined according to the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. After a median follow-up of 25.7 months, the median rPFS in the apalutamide plus AAP group was 22.6 months, versus 16.6 months in the placebo plus AAP group (HR 0.69; 95% CI 0.58–0.83; P<0.0001). These results equated to an extension of rPFS of 6 months and a 31% reduction in risk of rPFS in chemotherapy-naïve mCRPC patients.

Secondary outcomes were overall survival, prostate-specific antigen (PSA) response, time to initiation of opioid use, time to initiation of chemotherapy, and time to pain progression (as measured by the Brief pain inventory-short form scale). The first interim analysis for overall survival also occurred after a median period of 25.7 months, and the apalutamide plus AAP treatment arm showed a longer median OS than the placebo plus AAP treatment arm, although not statistically significant. The apalutamide plus AAP group demonstrated a significantly higher rate of ≥50% decline in PSA compared with placebo plus AAP (RR 1.09; 95% CI 1.02–1.17; P=0.015). Time to PSA response, time to initiation of opioid use, time to initiation of chemotherapy, and time to pain progression did not differ significantly between the 2 treatment groups.

In terms of treatment-emergent adverse events, 310/490 (63.3%) participants in the apalutamide plus AAP group reported grade 3 to 4 adverse events, compared with 275/489 (56.2%) participants in the placebo plus AAP group. No new safety concerns were identified.

1. Rathkopf D. Final results from ACIS, a randomised, placebo-controlled double-blind phase 3 study of apalutamide and abiraterone acetate plus prednisone (AAP) versus AAP in patients with chemo-naive metastatic castration-resistant prostate cancer (mCRPC). Abstract 9, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March 202117 May 2024